Investigating the impact of RF saturation-pulse parameters on compartment-selective gas-phase depolarization with xenon polarization transfer contrast MRI.

PURPOSE: To demonstrate the utility of continuous-wave (CW) saturation pulses in xenon-polarization transfer contrast (XTC) MRI and MRS, to investigate the selectivity of CW pulses applied to dissolved-phase resonances, and to develop a correction method for measurement biases from saturation of the nontargeted dissolved-phase compartment. METHODS: Studies were performed in six healthy Sprague-Dawley rats over a series of end-exhale breath holds. Discrete saturation schemes included a series of 30 Gaussian pulses (8 ms FWHM), spaced 25 ms apart; CW saturation schemes included single block pulses, with variable flip angle and duration. In XTC imaging, saturation pulses were applied on both dissolved-phase resonance frequencies and off-resonance, to correct for other sources of signal loss and compromised selectivity. In spectroscopy experiments, saturation pulses were applied at a set of 19 frequencies spread out between 185 and 200 ppm to map out modified z-spectra. RESULTS: Both modified z-spectra and imaging results showed that CW RF pulses offer sufficient depolarization and improved selectivity for generating contrast between presaturation and postsaturation acquisitions. A comparison of results obtained using a variety of saturation parameters confirms that saturation pulses applied at higher powers exhibit increased cross-contamination between dissolved-phase resonances. CONCLUSION: Using CW RF saturation pulses in XTC contrast preparation, with the proposed correction method, offers a potentially more selective alternative to traditional discrete saturation. The suppression of the red blood cell contribution to the gas-phase depolarization opens the door to a novel way of quantifying exchange time between alveolar volume and hemoglobin.

Radial Flow Perfusion Enables Real-Time Profiling of Cellular Metabolism at Low Oxygen Levels with Hyperpolarized 13C NMR Spectroscopy.

In this study, we describe new methods for studying cancer cell metabolism with hyperpolarized 13C magnetic resonance spectroscopy (HP 13C MRS) that will enable quantitative studies at low oxygen concentrations. Cultured hepatocellular carcinoma cells were grown on the surfaces of non-porous microcarriers inside an NMR spectrometer. They were perfused radially from a central distributer in a modified NMR tube (bioreactor). The oxygen level of the perfusate was continuously monitored and controlled externally. Hyperpolarized substrates were injected continuously into the perfusate stream with a newly designed system that prevented oxygen and temperature perturbations in the bioreactor. Computational and experimental results demonstrated that cell mass oxygen profiles with radial flow were much more uniform than with conventional axial flow. Further, the metabolism of HP [1-13C]pyruvate was markedly different between the two flow configurations, demonstrating the importance of avoiding large oxygen gradients in cell perfusion experiments.

Metabolic Imaging and Biological Assessment: Platforms to Evaluate Acute Lung Injury and Inflammation.

Pulmonary inflammation is a hallmark of several pulmonary disorders including acute lung injury and acute respiratory distress syndrome. Moreover, it has been shown that patients with hyperinflammatory phenotype have a significantly higher mortality rate. Despite this, current therapeutic approaches focus on managing the injury rather than subsiding the inflammatory burden of the lung. This is because of the lack of appropriate non-invasive biomarkers that can be used clinically to assess pulmonary inflammation. In this review, we discuss two metabolic imaging tools that can be used to non-invasively assess lung inflammation. The first method, Positron Emission Tomography (PET), is widely used in clinical oncology and quantifies flux in metabolic pathways by measuring uptake of a radiolabeled molecule into the cells. The second method, hyperpolarized 13C MRI, is an emerging tool that interrogates the branching points of the metabolic pathways to quantify the fate of metabolites. We discuss the differences and similarities between these techniques and discuss their clinical applications.

Quantification of Ventilation and Gas Uptake in Free-Breathing Mice With Hyperpolarized 129Xe MRI.

Hyperpolarized 129Xe magnetic resonance imaging is a powerful modality capable of assessing lung structure and function. While it has shown promise as a clinical tool for the longitudinal assessment of lung function, its utility as an investigative tool for animal models of pulmonary diseases is limited by the necessity of invasive intubation and mechanical ventilation procedures. In this paper, we overcame this limitation by developing a gas delivery system and implementing a set of imaging schemes to acquire high-resolution gas- and dissolved-phase images in free-breathing mice. Gradient echo pulse sequences were used to acquire both high- and low-resolution gas-phase images, and regional fractional ventilation was quantified by comparing signal buildup among low-resolution gas-phase images acquired at two flip-angles. Dissolved-phase images were acquired using both ultra-short echo time and chemical shift imaging sequences with discrete sets of flip-angle/repetition time combinations to visualize gas uptake and distribution throughout the body. Spectral features distinct to various anatomical regions were identified in images acquired using the latter sequence and were used for the quantification of gas arrival times for respective compartments.

Multibreath Hyperpolarized 3He Imaging Scheme to Measure Alveolar Oxygen Tension and Apparent Diffusion Coefficient.

RATIONALE AND OBJECTIVES: In this study, we compared a newly developed multibreath simultaneous alveolar oxygen tension and apparent diffusion coefficient (PAO2-ADC) imaging sequence to a single-breath acquisition, with the aim of mitigating the compromising effects of intervoxel flow and slow-filling regions on single-breath measurements, especially in chronic obstructive pulmonary disease (COPD) subjects. MATERIALS AND METHODS: Both single-breath and multibreath simultaneous PAO2-ADC imaging schemes were performed on a total of 10 human subjects (five asymptomatic smokers and five COPD subjects). Estimated PAO2 and ADC values derived from the different sequences were compared both globally and regionally. The distribution of voxels with nonphysiological values was also compared between the two schemes. RESULTS: The multibreath protocol decreased the ventilation defect volumes by an average of 12.9 ± 6.6%. The multibreath sequence generated nonphysiological PAO2 values in 11.0 ± 8.5% fewer voxels than the single-breath sequence. Single-breath PAO2 maps also showed more regions with gas-flow artifacts and general signal heterogeneity. On average, the standard deviation of the PAO2 distribution was 16.5 ± 7.0% lower using multibreath PAO2-ADC imaging, suggesting a more homogeneous gas distribution. Both mean and standard deviation of the ADC increased significantly from single- to multibreath imaging (p = 0.048 and p = 0.070, respectively), suggesting more emphysematous regions in the slow-filling lung. CONCLUSION: Multibreath PAO2-ADC imaging provides superior accuracy and efficiency compared to previous imaging protocols. PAO2 and ADC maps generated by multibreath imaging allowed for the qualification of various regions as emphysematous or obstructed, which single-breath PAO2 maps can only identify as defects. The simultaneous PAO2 and ADC measurements generated by the presented multibreath method were also more physiologically realistic, and allowed for more detailed analysis of the slow-filling regions characteristic of COPD subjects.

A Model for Predicting Future FEV1 Decline in Smokers Using Hyperpolarized 3He Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: The purpose of this study was to assess the effectiveness of hyperpolarized helium-3 magnetic resonance (MR)-based imaging markers in predicting future forced expiratory volume in one second decline/chronic obstructive pulmonary disorder progression in smokers compared to current diagnostic techniques. MATERIALS AND METHODS: Total 60 subjects (15 nonsmokers and 45 smokers) participated in both baseline and follow-up visits (∼1.4 years apart). At both visits, subjects completed pulmonary function testing, a six-minute walk test , and the St. George Respiratory Questionnaire. Using helium-3 MR imaging, means (M) and standard deviations (H) of oxygen tension (PAO2), fractional ventilation, and apparent diffusion coefficient were calculated across 12 regions of interest in the lungs. Subjects who experienced FEV1 decline >100 mL/year were deemed "decliners," while those who did not were deemed "sustainers." Nonimaging and imaging prediction models were generated through a logistic regression model, which utilized measurements from sustainers and decliners. RESULTS: The nonimaging prediction model included the St. George Respiratory Questionnaire total score, diffusing capacity of carbon monoxide by the alveolar volume (DLCO/VA), and distance walked in a six-minute walk test. A receiving operating character curve for this model yielded a sensitivity of 75% and specificity of 68% with an overall area under the curve of 65%. The imaging prediction model generated following the same methodology included ADCH, FVH, and PAO2H. The resulting receiving operating character curve yielded a sensitivity of 87.5%, specificity of 82.8%, and an area under the curve of 89.7%. CONCLUSION: The imaging predication model generated from measurements obtained during 3He MR imaging is better able to predict future FEV1 decline compared to one based on current clinical tests and demographics. The imaging model's superiority appears to arise from its ability to distinguish well-circumscribed, severe disease from a more uniform distribution of moderately altered lung function, which is more closely associated with subsequent FEV1 decline.

In vivo imaging of the progression of acute lung injury using hyperpolarized [1-13 C] pyruvate.

PURPOSE: To investigate pulmonary metabolic alterations during progression of acute lung injury. METHODS: Using hyperpolarized [1-13 C] pyruvate imaging, we measured pulmonary lactate and pyruvate in 15 ventilated rats 1, 2, and 4 h after initiation of mechanical ventilation. Lung compliance was used as a marker for injury progression. 5 untreated rats were used as controls; 5 rats (injured-1) received 1 ml/kg and another 5 rats (injured-2) received 2 ml/kg hydrochloric acid (pH 1.25) in the trachea at 70 min. RESULTS: The mean lactate-to-pyruvate ratio of the injured-1 cohort was 0.15 ± 0.02 and 0.15 ± 0.03 at baseline and 1 h after the injury, and significantly increased from the baseline value 3 h after the injury to 0.23 ± 0.02 (P = 0.002). The mean lactate-to-pyruvate ratio of the injured-2 cohort decreased from 0.14 ± 0.03 at baseline to 0.08 ± 0.02 1 h after the injury and further decreased to 0.07 ± 0.02 (P = 0.08) 3 h after injury. No significant change was observed in the control group. Compliance in both injured groups decreased significantly after the injury (P < 0.01). CONCLUSIONS: Our findings suggest that in severe cases of lung injury, edema and hyperperfusion in the injured lung tissue may complicate interpretation of the pulmonary lactate-to-pyruvate ratio as a marker of inflammation. However, combining the lactate-to-pyruvate ratio with pulmonary compliance provides more insight into the progression of the injury and its severity. Magn Reson Med 78:2106-2115, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Regional Fractional Ventilation by Using Multibreath Wash-in (3)He MR Imaging.

Purpose To assess the feasibility and optimize the accuracy of the multibreath wash-in hyperpolarized helium 3 ((3)He) approach to ventilation measurement by using magnetic resonance (MR) imaging as well as to examine the physiologic differences that this approach reveals among nonsmokers, asymptomatic smokers, and patients with chronic obstructive pulmonary disease (COPD). Materials and Methods All experiments were approved by the local institutional review board and compliant with HIPAA. Informed consent was obtained from all subjects. To measure fractional ventilation, the authors administered a series of identical normoxic hyperpolarized gas breaths to the subject; after each inspiration, an image was acquired during a short breath hold. Signal intensity buildup was fit to a recursive model that regionally solves for fractional ventilation. This measurement was successfully performed in nine subjects: three healthy nonsmokers (one man, two women; mean age, 45 years ± 4), three asymptomatic smokers (three men; mean age, 51 years ± 5), and three patients with COPD (three men; mean age, 59 years ± 5). Repeated measures analysis of variance was performed, followed by post hoc tests with Bonferroni correction, to assess the differences among the three cohorts. Results Whole-lung fractional ventilation as measured with hyperpolarized (3)He in all subjects (mean, 0.24 ± 0.06) showed a strong correlation with global fractional ventilation as measured with a gas delivery device (R(2) = 0.96, P < .001). Significant differences between the means of whole-lung fractional ventilation (F2,10 = 7.144, P = .012) and fractional ventilation heterogeneity (F2,10 = 7.639, P = .010) were detected among cohorts. In patients with COPD, the protocol revealed regions wherein fractional ventilation varied substantially over multiple breaths. Conclusion Multibreath wash-in hyperpolarized (3)He MR imaging of fractional ventilation is feasible in human subjects and demonstrates very good global (whole-lung) precision. Fractional ventilation measurement with this physiologically realistic approach reveals significant differences between patients with COPD and healthy subjects. To minimize error, several sources of potential bias must be corrected when calculating fractional ventilation. (©) RSNA, 2016 Online supplemental material is available for this article.

Low-temperature dynamic nuclear polarization of gases in Frozen mixtures.

PURPOSE: To present a new cryogenic technique for preparing gaseous compounds in solid mixtures for polarization using dynamic nuclear polarization (DNP). METHODS: (129) Xe and (15) N2 O samples were prepared using the presented method. Samples were hyperpolarized at 1.42K at 5 Tesla. (129) Xe was polarized at 1.65K and 1.42K to compare enhancement. Polarization levels for both samples and T1 relaxation times for the (129) Xe sample were measured. Sample pulverization for the (129) Xe and controlled annealing for both samples were introduced as additional steps in sample preparation. RESULTS: Enhancement increased by 15% due to a temperature drop from 1.65K to 1.42K for the (129) Xe sample. A polarization level of 20 ± 3% for the (129) Xe sample was achieved, a two-fold increase from 10 ± 1% after pulverization of the sample at 1.42K. T1 of the (129) Xe sample was increased by more than three-fold by means of annealing. In the case of (15) N2 O, annealing led to a ∼two-fold increase in the signal level after DNP. CONCLUSION: The presented technique for producing and manipulating solid gas/glassing agent/radical mixtures for DNP led to high polarization levels in (129) Xe and (15) N2 O samples. These methods show potential for polarizing other gases using DNP technology. Magn Reson Med 76:1007-1014, 2016. © 2015 Wiley Periodicals, Inc.

Versatile pulse sequence device to conserve hyperpolarization for NMR and MRI studies.

PURPOSE: Levitt and co-workers have described the M2S pulse sequence which transfers between longitudinal and singlet spin order. Building on this work, we describe the construction of a portable M2S pulse sequence generator to increase the relaxation time of polarized compounds. Additionally, we investigate the efficiency of spin order transfer under conditions where physical parameters of the system are not known precisely. THEORY AND METHODS: A portable M2S generator is built. Longitudinally polarized N2O is converted to the singlet state by both adiabatic transfer and by the M2S sequence. Density matrix simulations are used to model the effects of mismatched chemical shift, flip angle, and scalar couplings. RESULTS: Density matrix simulations suggest that to convert 95% of the longitudinal m = 1 triplet state population to the singlet order we must match the Larmor precession frequency to the excitation radiofrequency field by 10%, the scalar couplings must be determined to better than 0.6%, and the flip angle must be calibrated to better than 2%. CONCLUSION: The sequence is robust against many mismatched physical parameters of the species we are converting. Additionally, the instrument's portability allows for the conversion of hyperpolarized species near a polarizer. The lifetime is increased by ∼12-fold. This is highly advantageous in systems where the hyperpolarized media relax rapidly.

Oxygen-weighted Hyperpolarized (3)He MR Imaging: A Short-term Reproducibility Study in Human Subjects.

PURPOSE: To determine whether hyperpolarized helium 3 magnetic resonance (MR) imaging to measure alveolar partial pressure of oxygen (Pao2) shows sufficient test-retest repeatability and between-cohort differences to be used as a reliable technique for detection of alterations in gas exchange in asymptomatic smokers. MATERIALS AND METHODS: The protocol was approved by the local institutional review board and was HIPAA compliant. Informed consent was obtained from all subjects. Two sets of MR images were obtained 10 minutes apart in 25 subjects: 10 nonsmokers (five men, five women; mean ± standard deviation age, 50 years ± 6) and 15 smokers (seven women, eight men; mean age, 50 years ± 8). A mixed-effects model was developed to identify the regional repeatability of Pao2 measurements as an intraclass correlation coefficient. Ten smokers were matched with the 10 nonsmokers on the basis of signal-to-noise ratio (SNR). Three separate models were generated: one for nonsmokers, one for the SNR-matched smokers, and one for the five remaining smokers, who were imaged with a significantly higher SNR. RESULTS: Short-term back-to-back regional reproducibility was assessed by using intraclass correlation coefficients, which were 0.67 and 0.65 for SNR case-matched nonsmokers and smokers, respectively. Repeatability was a strong function of SNR; a 50% increase in SNR in the remaining smokers improved the intraclass correlation coefficient to 0.82. Although repeatability was not significantly different between the SNR-matched cohorts (P = .44), the smoker group showed higher spatial and temporal variability in Pao2. CONCLUSION: The short-term test-retest repeatability of hyperpolarized gas MR imaging of regional Pao2 was good. Asymptomatic smokers exhibited greater spatial and temporal variability in Pao2 than did the nonsmokers, which suggests that this parameter allows detection of small functional alterations associated with smoking.

Efficient production of hyperpolarized bicarbonate by chemical reaction on a DNP precursor to measure pH.

PURPOSE: To produce hyperpolarized bicarbonate indirectly via chemical reaction from a hyperpolarized precursor and utilize it for the simultaneous regional measurement of metabolism and pH. METHODS: Alpha keto carboxylic acids are first hyperpolarized by dissolution dynamic nuclear polarization (DNP). These precursor molecules are rapidly reacted with hydrogen peroxide (H2O2) to decarboxylate the species, resulting in new target molecules. Unreacted H2O2 is removed from the system by reaction with sulfite. Interrogation of the ratio of dissolved carbon dioxide (CO2) to bicarbonate can be used to determine pH. RESULTS: Conversion of hyperpolarized alpha keto acids to bicarbonate and CO2 results in a minimal loss of the spin order. The reaction can be conducted to completion within seconds and preserves the nuclear spin polarization. CONCLUSION: Through a rapid chemical reaction, we can conserve the nuclear spin order of a DNP precursor to generate multiple hyperpolarized bioprobes otherwise unamenable to polarization. This indirect technique for the production of hyperpolarized agents can be applied to different precursor compounds to generate additional novel probes.

Alterations of regional alveolar oxygen tension in asymptomatic current smokers: assessment with hyperpolarized (3)He MR imaging.

PURPOSE: To assess the ability of helium 3 ((3)He) magnetic resonance (MR) imaging of regional alveolar partial pressure of oxygen (Pao2) to depict smoking-induced functional alterations and to compare its efficacy to that of current diagnostic techniques. MATERIALS AND METHODS: This study was approved by the local institutional review board and was compliant with HIPAA. All subjects provided informed consent. A total of 43 subjects were separated into three groups: nonsmokers, asymptomatic smokers, and symptomatic smokers. All subjects underwent a Pao2 imaging session followed by clinically standard pulmonary function tests (PFTs), the 6-minute walk test, and St George Respiratory Questionnaire (SGRQ). The whole-lung mean and standard deviation of Pao2 were compared with metrics derived from PFTs, the 6-minute walk test, and the SGRQ. A logistic regression model was developed to identify the predictors of alterations to the lungs of asymptomatic smokers. RESULTS: The whole-lung standard deviation of Pao2 correlated with PFT metrics (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC], Pearson r = -0.69, P < .001; percentage predicted FEV1, Pearson r = -0.67, P < .001; diffusing capacity of lung for carbon monoxide [Dlco], Pearson r = -0.45, P = .003), SGRQ score (Pearson r = 0.67, P < .001), and distance walked in 6 minutes (Pearson r = -0.47, P = .002). The standard deviation of Pao2 was significantly higher in asymptomatic smokers than in nonsmokers (change in the standard deviation of Pao2 = 7.59 mm Hg, P = .041) and lower when compared with symptomatic smokers (change in the standard deviation of Pao2 = 10.72 mm Hg, P = .001). A multivariate prediction model containing FEV1/FVC and the standard deviation of Pao2 (as significant predictors of subclinical changes in smokers) and Dlco (as a confounding variable) was formulated. This model resulted in an area under the receiver operating characteristic curve with a significant increase of 29.2% when compared with a prediction model based solely on nonimaging clinical tests. CONCLUSION: The (3)He MR imaging heterogeneity metric (standard deviation of Pao2) enabled the differentiation of all three study cohorts, which indicates that it can depict smoking-related functional alterations in asymptomatic current smokers.

Vertical gradients in regional alveolar oxygen tension in supine human lung imaged by hyperpolarized 3He MRI.

The purpose of this study was to evaluate whether regional alveolar oxygen tension (P(A)O2) vertical gradients imaged with hyperpolarized (3)He can identify smoking-induced pulmonary alterations. These gradients are compared with common clinical measurements including pulmonary function tests (PFTs), the six minute walk test, and the St. George's Respiratory Questionnaire. 8 healthy non-smokers, 12 asymptomatic smokers, and 7 symptomatic subjects with chronic obstructive pulmonary disease (COPD) underwent two sets of back-to-back P(A)O2 imaging acquisitions in the supine position in two opposite directions (top to bottom and bottom to top), followed by clinically standard pulmonary tests. The whole-lung mean, standard deviation (DP(A)O2) and vertical gradients of P(A)O2 along the slices were extracted, and the results were compared with clinically derived metrics. Statistical tests were performed to analyze the differences between cohorts. The anterior-posterior vertical gradients and DP(A)O2 effectively differentiated all three cohorts (p < 0.05). The average vertical gradient P(A)O2 in healthy subjects was -1.03 ± 0.51 Torr/cm toward lower values in the posterior/dependent regions. The directional gradient was absent in smokers (0.36 ± 1.22 Torr/cm) and was in the opposite direction in COPD subjects (2.18 ± 1.54 Torr/cm). The vertical gradients correlated with smoking history (p = 0.004); body mass index (p = 0.037), PFT metrics (forced expiratory volume in 1 s, p = 0.025; residual volume/total lung capacity percent predicted, p = 0.033) and with distance walked in 6 min (p = 0.009). Regional P(A)O2 data indicate that cigarette smoke induces physiological alterations that are not being detected by the most widely used physiological tests.

A variability study of regional alveolar oxygen tension measurement in humans using hyperpolarized (3) He MRI.

PURPOSE: A systematic study of the short-term and long-term variability of regional alveolar partial pressure of oxygen tension (pA O2 ) measurements using (3) He magnetic resonance imaging was presented. Additionally, the repeatability of the average evaluated pA O2 was compared with that of the standard pulmonary function tests. METHODS: Pulmonary function test and pA O2 imaging were performed on 4 nonsmokers (1 M, 3 F, 56 ± 1.7 years) and 4 smokers (3 M, 1 F, 52 ± 7.5 years) during three visits over the course of 2 weeks. Two measurements were performed per visit. Variability of pA O2 was assessed using a mixed-effect model, with an intraclass correlation coefficient calculated for each group. The coefficient of variation of pA O2 over the 3-day period was also compared with the coefficient of variation of pulmonary function test results. RESULTS: Short-term regional variability based on intraclass correlation coefficient was 0.71 for nonsmokers, and 0.63 for smokers, with long-term variability significantly lower at 0.59 and 0.47, respectively. While the coefficient of variation of the average pA O2 was similar to the repeatability of the diffusing capacity of CO, it was significantly higher than that of Forced Vital Capacity (P = 0.02). CONCLUSION: Short-term and long-term pA O2 variability differences were used as an indication of true physiological changes in order to measure technical reproducibility. Smokers show higher physiologic variability and less technical reproducibility. The suggested pA O2 -imaging technique showed a reasonable regional repeatability in nonsmokers as well as the ability to detect differences between the two groups with similar reproducibility and superior discriminatory ability when compared with pulmonary function tests.

Determination of the singlet state lifetime of dissolved nitrous oxide from high field relaxation measurements.

Longitudinal spin relaxation due to modulation of dipolar interactions often limits the development of hyperpolarized magnetic tracers. Recently, it has been demonstrated that transferring spin order to a singlet state significantly increases the polarization lifetimes in systems where nitrous oxide is dissolved in a liquid solvent. Additionally, previous studies have suggested that the longitudinal relaxation of nitrous oxide is largely dominated by the spin-rotation interaction. Models of spin-relaxation under Brownian motion naïvely predict the angular momentum reorienting correlation time of the spin rotation interaction to be inversely proportional to the viscosity of the solution. This dependence implies the singlet lifetime can be lengthened by increasing the dissolving solvent's viscosity-an extension which is not observed. Our work formulates a model which describes the relaxation of nitrous oxide dissolved in various solvents. We investigate the effect of altering the temperature of the solvent, as well as the effect of varying solute-solvent interactions on the singlet state as well as the longitudinal polarization lifetime. We predict the singlet lifetime for nitrous oxide dissolved in several solvents by fitting rotational and angular momentum correlation times measured at high magnetic field, and relate singlet relaxation to translational diffusion constants.

A multislice single breath-hold scheme for imaging alveolar oxygen tension in humans.

Reliable, noninvasive, and high-resolution imaging of alveolar partial pressure of oxygen (p(A)O(2)) is a potentially valuable tool in the early diagnosis of pulmonary diseases. Several techniques have been proposed for regional measurement of p(A)O(2) based on the increased depolarization rate of hyperpolarized (3) He. In this study, we explore one such technique by applying a multislice p(A)O(2) -imaging scheme that uses interleaved-slice ordering to utilize interslice time-delays more efficiently. This approach addresses the low spatial resolution and long breath-hold requirements of earlier techniques, allowing p(A)O(2) measurements to be made over the entire human lung in 10-15 s with a typical resolution of 8.3 × 8.3 × 15.6 mm(3). PO(2) measurements in a glass syringe phantom were in agreement with independent gas analysis within 4.7 ± 4.1% (R = 0.9993). The technique is demonstrated in four human subjects (healthy nonsmoker, healthy former smoker, healthy smoker, and patient with COPD), each imaged six times on 3 different days during a 2-week span. Two independent measurements were performed in each session, consisting of 12 coronal slices. The overall p(A)O(2) mean across all subjects was 95.9 ± 12.2 Torr and correlated well with end-tidal O(2) (R = 0.805, P < 0.0001). The alveolar O(2) uptake rate was consistent with the expected range of 1-2 Torr/s. Repeatable visual features were observed in p(A)O(2) maps over different days, as were characteristic differences among the subjects and gravity-dependent effects.

Improved technique for measurement of regional fractional ventilation by hyperpolarized 3He MRI.

Quantitative measurement of regional lung ventilation is of great significance in assessment of lung function in many obstructive and restrictive pulmonary diseases. A new technique for regional measurement of fractional ventilation using hyperpolarized 3He MRI is proposed, addressing the shortcomings of an earlier approach that limited its use to small animals. The new approach allows for the acquisition of similar quantitative maps over a shortened period and requires substantially less 3He gas. This technique is therefore a better platform for implementation in large species, including humans. The measurements using the two approaches were comparable to a great degree, as verified in a healthy rat lung, and are very reproducible. Preliminary validation is performed in a lung phantom system. Volume dependency of measurements was assessed both in vivo and in vitro. A scheme for selecting an optimum flip angle is proposed. In addition, a dead space modeling approach is proposed to yield more accurate measurements of regional fractional ventilation using either method. Finally, sensitivity of the new technique to model parameters, noise, and number of included images were assessed numerically. As a prelude to application in humans, the technique was implemented in a large animal study successfully.